title: Donor-specific antibody against denatured HLA-A1: clinically nonsignificant?
abstract: Pre-transplant screening of a woman with end-stage renal disease (ESRD) showed no anti-human leukocyte antigen (HLA) alloantibodies by anti-human globulin-complement-dependent cytotoxicity (AHG-CDC; class I) or enzyme-linked immunosorbent assay (class II). Following a negative AHG-CDC crossmatch, an HLA*01:01+ deceased donor (DD) kidney was transplanted in September 2005. Subsequent screening of pre-transplant serum by LABScreen Single Antigen (SA) array showed strong reactivity versus A*01:01. Despite that reactivity, at 5 years post-transplant, the patient has a serum creatinine of 1.6 mg/dl and has never experienced humoral or cellular rejection. Retrospective flow-cytometric crossmatch of pre- and post-transplant sera versus DD cells was negative. Rescreening of multiple pre- and post-transplant sera revealed anti-A1 reactivity persisting from the first through the last samples tested. The patient's anti-A1 was almost two fold more reactive with denatured A*01:01 FlowPRA SA beads after denaturation with acid treatment (pH 2.7) than with untreated beads. Parallel results were observed with pH 2.7 treated versus untreated A1+ T cells in FXM. These data highlight the difficulty in interpreting screening results obtained using bead arrays, because of antibodies that appear to recognize denatured but not native class I HLA antigens. We suggest that such bead-positive, flow cytometric crossmatch negative antibodies are not associated with humoral rejection, may not necessarily be detrimental to a graft, and deserve further evaluation before becoming a barrier to transplantation.
authors.affiliation: Seattle Cancer Care Alliance, Clinical Research Division, Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA. spereira@seattlecca.org
authors.forename: Shalini
authors.initials: S
authors.lastname: Pereira
authors.forename: Susan
authors.initials: S
authors.lastname: Perkins
authors.forename: Jar-How
authors.initials: JH
authors.lastname: Lee
authors.forename: Wayne
authors.initials: W
authors.lastname: Shumway
authors.forename: William
authors.initials: W
authors.lastname: LeFor
authors.forename: Mayra
authors.initials: M
authors.lastname: Lopez-Cepero
authors.forename: Cynthia
authors.initials: C
authors.lastname: Wong
authors.forename: Amy
authors.initials: A
authors.lastname: Connolly
authors.forename: Jane C
authors.initials: JC
authors.lastname: Tan
authors.forename: F Carl
authors.initials: FC
authors.lastname: Grumet
mesh_terms: D001788:Blood Grouping and Crossmatching; D002469:Cell Separation; D003404:Creatinine / Q000097:blood; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D015788:HLA-A1 Antigen; D006650:Histocompatibility Testing; D006801:Humans; D056724:Immunity, Humoral; D007518:Isoantibodies / Q000097:blood; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000628:therapy*; D016030:Kidney Transplantation; D011489:Protein Denaturation; D014181:Transplantation Immunology; D023001:Transplantation Tolerance
chemical_list: D015234:HLA-A Antigens; C506470:HLA-A*01:01 antigen; D015788:HLA-A1 Antigen; D007518:Isoantibodies; D003404:Creatinine